The presence and concentration of analytes, as well as the progress and efficiency of chemical reactions, are typically measured directly—e.g., through optical monitoring if a reaction produces an observable change in light-absorption characteristics, or indirectly—e.g., by changes in mass or volume. Many of the methods typically employed require attachment of a label compound whose properties (i.e., fluorescent, radioactive, chemiluminescent, or absorbing) enable sensitive detection. These methods, however, require development of label reagents, add steps to the detection process, and modify the analyte. In the absence of label compounds, conventional measurements operate on a gross scale, and as a result require substantial amounts of analyte.
Enhanced sensitivity has recently been achieved using small micromachined cantilevers and flexural plate wave (FPW) sensors to facilitate monitoring chemical reactions and interactions on a microscopic scale. In the cantilever, the reaction is transduced into mechanical stresses. These stresses are detected with a high degree of sensitivity. Cantilever arrangements can be difficult to manufacture and operate due to the small size and fragility of the fingers, however, and to the need to separate analytes from the readout mechanism. Because the cantilevers are delicate, applying selective coatings can be difficult. To separate the analytes from readout electronics, optical readouts usually employing reflection may be employed. Cantilever-based approaches have achieved success primarily in specialized laboratories with personnel trained to handle the nuances of such devices.
FPW systems may utilize a diaphragm that is acoustically excited by interdigitated fingers to establish a standing wave pattern. The diaphragm is coated with the selective material, and interaction of analytes with the coating increases the effective thickness of the diaphragm, thereby affecting the frequency of the standing wave so as to indicate the degree of interaction. Because these devices are constructed of conducting, mechanical, and piezoelectric layers, bimetallic effects can produce unwanted temperature sensitivity. To reduce thermal distortions, FPW sensors are typically run at high resonant frequencies. Unfortunately, the high operating frequency itself limits sensitivity (in addition to requiring somewhat complex electronics).